A Disorder-to-Order Transition Activates an ATP-Independent Membrane Protein Chaperone. Issue 24 (4th December 2020)

• Record Type: Journal Article
• Authors: Siegel, Alex; McAvoy, Camille Z.; Lam, Vinh; Liang, Fu-Cheng; Kroon, Gerard; Miaou, Emily; Griffin, Patrick; Wright, Peter E.; Shan, Shu-ou
• Is Part Of: Journal of molecular biology. Volume 432:Issue 24(2020)
• Publication Date: 2020-12-04
• Subjects: chaperone -- membrane protein biogenesis -- protein dynamics -- ankyrin repeat proteins -- NMR spectroscopy; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2020.11.007
• Languages: English
• ISSNs: 0022-2836

Abstract

Graphical abstract: Highlights: Substrate and activator drive cpSRP43 from an inactive, open state to an active, closed state. The open state is characterized by disordered Ankyrin repeat motifs in the client binding domain. Activator binding drives a disorder-to-order transition in the Ankyrin repeat domain. The bridging helix mediates allosteric communication from ligand binding to the client binding domain. Abstract: The 43 kDa subunit of the chloroplast signal recognition particle, cpSRP43, is an ATP-independent chaperone essential for the biogenesis of the light harvesting chlorophyll-binding proteins (LHCP), the most abundant membrane protein family on earth. cpSRP43 is activated by a stromal factor, cpSRP54, to more effectively capture and solubilize LHCPs. The molecular mechanism underlying this chaperone activation is unclear. Here, a combination of hydrogen–deuterium exchange, electron paramagnetic resonance, and NMR spectroscopy experiments reveal that a disorder-to-order transition of the ankyrin repeat motifs in the substrate binding domain of cpSRP43 drives its activation. An analogous coil-to-helix transition in the bridging helix, which connects the ankyrin repeat motifs to the cpSRP54 binding site in the second chromodomain, mediates long-range allosteric communication of cpSRP43 with its activating binding partner. Our results provide a molecular model to explain how the conformational dynamics of cpSRP43 enables regulation of its chaperone activity and suggest a general mechanism by which ATP-independent chaperones with cooperatively folding domains can be regulated.